m-Amino-phenylimino-imidazolidine derivatives for treating urinary incontinence

Abstract

A compound of Formula I or of Formula IIwherein:R1 is F, Cl, Br, CH2F, CF2H, or CF3;R2 is NR6R7, where R6 is Me, Et, Pr, or iPr, and R7 is Me, Et or Pr; andR3, R4, and R5 independently of one another each are H, Me, F, Cl, Br, CH2F, CF2H, or CF3,and if R4 is Me, F, Cl, Br, CH2F, CF2H, or CF3, then R1 is additionally H or Me, or a pharmacologically acceptable salt thereof. In addition, pharmaceutical compositions comprising an effective amount of these compounds, methods for the treatment or prophylaxis of urinary incontinence and diseases of the bladder using these compounds, and methods for making these compounds are disclosed.

We claim:  
     
       1. A compound of Formula I or of Formula II                    
       wherein: 
       R 1  is F, Cl, Br, CH 2 F, CF 2 H, or CF 3 ;  
       R 2  is NR 6 R 7 , where R 6  is Me, Et, Pr, or iPr, and R 7  is Me, Et or Pr;  
       R 3  is Me, F, Cl, Br, CH 2 F, CF 2 H, or CF 3 ;  
       R 4  and R 5  are each independently H, Me, F, Cl, Br, CH 2 F, CF 2 H, or CF 3 , and if R 4  is Me, F, Cl, Br, CH 2 F, CF 2 H, or CF 3 , then R 1  is additionally H or Me,  
       or a pharmacologically acceptable salt thereof.  
     
     
       2. A compound of Formula I or of Formula II                    
       wherein: 
       R 1  is H, Me, F, Cl, Br, CH 2 F, CF 2 H, or CF 3 ;  
       R 2  is NR 6 R 7 , where R 6  is Me, Et, Pr, or iPr, and R 7  is Me, Et or Pr;  
       R 3  and R 5  are each independently H, Me, F, Cl, Br, CH 2 F, CF 2 H, or CF 3 ; and  
       R 4  is Me, F, Cl, Br, CH 2 F, CF 2 H, or CF 3 ; or a pharmacologically acceptable salt thereof.  
     
     
       3. A compound of Formula I or of Formula II                    
       wherein: 
       R 1  is H, Me, F, Cl, Br, CH 2 F, CF 2 H, or CF 3 ;  
       R 2  is NR 6 R 7 , where R 6  is Me, Et, Pr, or iPr, and R 7  is Me, Et or Pr;  
       R 3  and R 4  are each independently Me, F, CI, Br, CH 2 F, CF 2 H, or CF 3 ;  
       R 5  is H, Me, F, Cl, Br, CH 2 F, CF 2 H, or CF 3 ,  
       or a pharmacologically acceptable salt thereof.  
     
     
       4. A compound of Formula I or of Formula II                    
       wherein: 
       R 1  is H, Me, F, Cl, Br, CH 2 F, CF 2 H, or CF 3 ;  
       R 2  is NR 6 R 7 , where R 6  is Me, Et, Pr, or iPr, and R 7  is Me, Et or Pr;  
       R 3  is H, Me, F, Cl, Br, CH 2 F, CF 2 H, or CF 3 ; and  
       R 4  and R 5  are each independently Me, F, Cl, Br, CH 2 F, CF 2 H, or CF 3 ;  
       or a pharmacologically acceptable salt thereof.  
     
     
       5. A compound of Formula I or of Formula II                    
       wherein: 
       R 1  is H, Me, F, Cl, Br, CH 2 F, CF 2 H, or CE 3 ;  
       R 2  is NR 6 R 7 , where R 6  is Me, Et, Pr, or iPr, and R 7  is Me, Et or Pr;  
       R 3  and R 5  are each independently Me, F, Cl, Br, CH 2 F, CF 2 H, or CF 3 ; and  
       R 4  is H, Me, F, Cl, Br, CH 2 F, CF 2 H, or CF 3 , and if R 4  is Me, F, Cl, Br, CH 2 F, CF 2 H, or CE 3 , then R 1  is additionally H or Me,  
       or a pharmacologically acceptable salt thereof.  
     
     
       6. A compound of Formula I or of Formula II                    
       wherein: 
       R 1  is H, Me, F, Cl, Br, CH 2 F, CF 2 H, or CE 3 ;  
       R 2  is NR 6 R 7 , where R 6  is Me, Et, Pr, or iPr, and R 7  is Me, Et or Pr; and  
       R 3 , R 4 , and R 5  are each independently Me, F, Cl, Br, CH 2 F, CF 2 H, or CE 3 ,  
       or a pharmacologically acceptable salt thereof.  
     
     
       7. A compound of Formula I or of Formula II                    
       wherein: 
       R 1  is H, Me, F, Cl, Br, or CF 3 ;  
       R 2  is NR 6 R 7 ;  
       R 3  and R 5  are each independently H, F, Cl, Br, or CF 3 ;  
       R 4  is F, Cl, Br, or CF 3 ; and  
       R 6  and R 7  are each independently Me or Et.  
     
     
       8. The compound according to  claim 7 , wherein: 
       R 1  is Me; R 3  is H, F, Br, or CF 3 ;  
       R 4  is Cl, Br, or CF 3 ; and  
       R 5  is H, Br, or CF 3 .  
     
     
       9. The compound according to  claim 8 , wherein: 
       R 1 , R 6 , and R 7  are each Me;  
       R 3  is H or F;  
       R 4  is Cl or Br; and  
       R 5  is H or Br.  
     
     
       10. The compound according to  claim 7 , wherein: 
       R 1  is F, Cl, Br, or CF 3 ;  
       R 3 , R 4 , and R 5  are each independently H, F, Cl, Br, or CF 3 ; and  
       R 6  and R 1  are each independently Me or Et.  
     
     
       11. The compound according to  claim 7 , wherein: 
       R 1  is Cl, Br, or CF 3 ;  
       R 3  is H, F, Br, or CF 3 ; and  
       R 5  is H, Br, or CF 3 .  
     
     
       12. The compound according to  claim 7 , wherein: 
       R 1  is Cl or Br;  
       R 3  is H or F;  
       R 5  is H or Br;  
       R 6  and R 7  are each Me.  
     
     
       13. A compound selected from the group consisting of: 
       (a) 2′-bromo-3′-chloro-5′-dimethylamino-6′-methylphen-1′-yl-2-iminoimidazolidine;  
       (b) 3′-bromo-5′-dimethylamino-6′-methylphen-1′-yl-2-iminoimidazolidine;  
       (c) 3′-bromo-5′-dimethylamino-6′-methylphen-1′-yl-2-iminoimidazolidine;  
       (d) 3′-chloro-5′-dimethylamino-6′-methylphen-1′-yl-2-iminoimidazolidine;  
       (e) 2′-3′-dibromo-5′-dimethylamino-6′-methylphen-1′-yl- 2- iminoimidazolidine;  
       (f) 2′-chloro-3′-dimethylaminophen-1′-yl-2-iminoimidazolidine  
       (g) 4′-bromo-2′-chloro-3′-dimethylaminophen-1′-yl-2-iminoimidazolidine;  
       (h) 2′-bromo-6′-chloro-5′-dimethylaminophen-1′-yl-2-iminoimidazolidine; and  
       (i) 5′-bromo-2′-chloro-3′-dimethylaminophen-1′-yl-2-iminoimidazolidine,  
       or a tautomer thereof or a corresponding pharmacologically-compatible salt thereof.  
     
     
       14. A compound selected from the group consisting of: 
       (a) 2′-bromo-3′-chloro-5′-dimethylamino-6′-methylphen-1′-yl-2-iminoimidazolidine;  
       (b) 3′-bromo-5′-dimethylamino-6′-methylphen-1′-yl-2-iminoimidazolidine;  
       (c) 3′-chloro-5′-dimethylamino-6′-methylphen-1′-yl-2-iminoimidazolidine; and  
       (d) 2′-3′-dibromo-5′-dimethylamino-6′-methylphen-1-yl-2-iminoimidazolidine;  
       or a tautomer thereof or a corresponding pharmacologically-compatible salt thereof.  
     
     
       15. 3′-chloro-5′-dimethylamino-6′-methylphen-1′-yl-2-iminiomidazolidine, or a tautomer thereof or a corresponding pharmacologically-compatible salt thereof. 
     
     
       16. 2′-chloro-3′-dimethylaminophen-1′-yl-2-iminoimidazolidine, or a tautomer thereof or a corresponding pharmacologically-compatible salt thereof. 
     
     
       17. 4′-bromo-2′-chloro-3′-dimethylaminophen-1′-yl-2-iminoimidazolidine, or a tautomer thereof or a corresponding pharmacologically-compatible salt thereof. 
     
     
       18. The compound of Formula I or of Formula II according to one of claims  1 ,  2 ,or  3 , to  7 , wherein the compound of Formula I or of Formula II is an imino-imidazolidine. 
     
     
       19. The compound of Formula I or of Formula II according to one of claims  1 ,  2 , or  3 , to  7 , wherein the compound of Formula I or of Formula II is an amino-imidazoline. 
     
     
       20. A pharmaceutical composition comprising an effective amount of a compound of Formula I or of Formula II according to one of claims  1 ,  2 , or  3 , to  7 , and an inert carrier or diluent. 
     
     
       21. A pharmaceutical composition comprising an effective amount of a compound of Formula I or of Formula II according to  claim 18  and an inert carrier or diluent. 
     
     
       22. A pharmaceutical composition comprising an effective amount of a compound of Formula I or of Formula II according to  claim 19  and an inert carrier or diluent.